The Study of Osteoporotic Fractures (SOF) is a multicenter prospective study of this important source of disability in a cohort of 9,704 women over age 65. Three examinations have yielded a comprehensive set of measurements that include bone mineral density (BMD), neuromuscular function, functional status, and other risk factors for fractures; follow-up over 2.7 years has been 99% complete. Among the many findings of SOF are the demonstration that appendicular BMD predicts hip and other types of fractures; the description of the risk factors for wrist and humerus fractures; the observation that the two types of hip fractures (cervical and intertrochanteric) have different relationships to bone density; and the discovery that women with low bone density have an increased risk of death from stroke. We propose to continue SOF to answer additional questions about fractures in women. A Year 5 Exam and continued follow-up will allow us to test the ability of ultrasound to predict fractures and determine whether it adds information on fracture risk to that provided by densitometry. At the Year 5 Exam we will also measure calcium absorption to test the hypothesis that it is associated with more rapid bone loss and more fractures. Updated measures of bone density, functional status, and neuromuscular function will provide values proximate to subsequent fractures and allow us to examine rate of change as a predictor of hip and other fractures. Continued follow-up will also allow a test of the hypothesis that intertrochanteric and cervical fractures of the hip have different risk factors. To study biochemical antecedents of fracture, we will use serum stored at -190 degrees Celsius since the baseline examination; we have demonstrated that hon-none levels have remained stable in these samples over 3.5 years. We will examine the levels of hormones, growth factors, and markers of bone turnover as predictors of subsequent hip, wrist, and vertebral fractures. Using an efficient nested case-cohort approach we will test, for example, whether women with low levels of 25(OH)Vitamin D have an increased risk of hip fracture. The strengths of SOF include its large sample of well-characterized older women, its prospective design with excellent rates of follow-up, its comprehensive measurements of bone mass and neuromuscular function, and its stable bank of frozen sera. Continued study of this unique cohort is likely to produce important advances in understanding and preventing fractures in older women.